The imaging characteristics of maximum likelihood (ML) reconstruction using the EM algorithm for emission tomography have been extensively evaluated. There has been less study of the precision and accuracy of ML estimates of regional radioactivity concentration. The authors developed a realistic brain slice simulation by segmenting a normal subject's MRI scan into gray matter, white matter, and CSF and produced PET sinogram data with a model that included detector resolution and efficiencies, attenuation, scatter, and randoms. Noisy realizations at different count levels were created, and ML and filtered backprojection (FBP) reconstructions were performed. The bias and variability of ROI values were determined. In addition, the effects of ML pixel size, image smoothing and region size reduction were assessed. Hit estimates at 3,000 iterations (0.6 sec per iteration on a parallel computer) for 1-cm(2) gray matter ROIs showed negative biases of 6%+/-2% which can be reduced to 0%+/-3% by removing the outer 1-mm rim of each ROI. FBP applied to the full-size ROIs had 15%+/-4% negative bias with 50% less noise than hit. Shrinking the FBP regions provided partial bias compensation with noise increases to levels similar to ML. Smoothing of ML images produced biases comparable to FBP with slightly less noise. Because of its heavy computational requirements, the ML algorithm will be most useful for applications in which achieving minimum bias is important.